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      Treatment resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology

      research-article
      , M.R.C.Psych., Ph.D, , M.R.C.Psych., , M.D., , M.D., Ph.D., , M.D., Ph.D., , M.D., , Ph.D., MA, BM BCh, MRCPsych., , M.D., Ph.D., , M.D., , M.D., , FRCPsych., , M.D., MPH., , M.D., Ph.D., FRCP(c)., , M.D., , MRCPsych, Ph.D., , M.D., Ph.D., FRCP., , M.D., Ph.D., , M.D., Ph.D., , M.D., Ph.D., , M.D., , M.D., Ph.D., , MB, M.D., FRCPI, FRCPsych., , M.D., Dr.Med.Sci., , M.D., Ph.D., , M.D, Ph.D., , M.D. FRCPC., , M.D, Ph.D., , M.D., , M.D. FRCPsych., , MBBS, MMed, MCI, FAMS, , M.D., , M.R.C.Psych., Ph.D, , BSc, PGDipSci, MHSc., , M.D., , , M.D., Ph.D., , MB BS, M.D. (Melb), Hon MD (Athens), MRCPsych, FRANZCP., , M.D., Ph.D., , M.D., Ph.D., , Ph.D., , BPharm, Ph.D, , Ph.D., , MD, Ph.D., , Mf, Ph.D., , BSc., MSc., Ph.D., FFRPS., FRPharmS., , DClinPsy., , M.D., , M.D., , BM, Ph.D., , M.D., , M.D.
      The American journal of psychiatry

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          Abstract

          Objective

          Treatment resistance complicates the management of schizophrenia. Research and clinical translation is limited by inconsistent definitions. To address this we evaluated current approaches and then developed consensus criteria and guidelines.

          Method

          A systematic review of randomized antipsychotic clinical trials in treatment resistant schizophrenia was performed. Definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed by a working group of researchers and clinicians through i) a multi-phase, mixed methods approach; ii) identifying key criteria via an online survey; and iii) meetings to achieve consensus.

          Results

          42 studies met inclusion criteria. Of these, 21 (50%) studies did not provide operationalized criteria, whilst in others, criteria varied considerably, particularly regarding symptom severity, prior treatment duration and antipsychotic dose thresholds. Important for the inability to compare results, only two (5%) studies utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) ≥moderate functional impairment; 3) prior treatment consisting of ≥2 different antipsychotic trials, each for a minimum duration and dose; 4) adherence systematically assessed and meeting minimum criteria; 5) ideally at least one prospective treatment trial; 6) criteria that clearly separated responsive from treatment resistant patients.

          Conclusions

          There is considerable variation in current approaches to defining treatment resistance in schizophrenia. We present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment and treatment response in schizophrenia, providing a benchmark for research and clinical translation.

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          Author and article information

          Journal
          0370512
          457
          Am J Psychiatry
          Am J Psychiatry
          The American journal of psychiatry
          0002-953X
          1535-7228
          6 November 2018
          06 December 2016
          01 March 2017
          12 November 2018
          : 174
          : 3
          : 216-229
          Affiliations
          Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK, SE5 8AF and The Zucker Hillside Hospital, Department of Psychiatry, Psychiatry Research, 75-59 263rd Street, Glen Oaks, New York 11004, USA
          Author notes
          Article
          PMC6231547 PMC6231547 6231547 ems80413
          10.1176/appi.ajp.2016.16050503
          6231547
          27919182
          caf9d16d-aad3-4ffb-a956-561b157ca0f8
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